Non-medical use of prescription drugs (NMUPD), i.e. opioids, tranquilizers, or stimulants, is a serious and growing public health problem in the U.S. Most data on NMUPD among young adults is limited to the heterosexual college population while significant knowledge gaps exist regarding NMUPD among young men who have sex with men (YMSM). Given the well-established intersection of drug use and risky sexual behaviors and high rates of HIV infections in YMSM, the purpose of this study is to examine the relationship between these drugs and physical, sexual and psychological health of YMSM. YMSM have unique concerns for health risks, such as depression, suicide, bullying, victimization, homelessness, and homophobia, but little is known of their intersection with NMUPD. Many YMSM experience normative pressures that encourage risky behaviors. At the same time, some forms of social support and resilience may buffer against negative effects of stressors. Significant gaps exist in our understanding of how these factors relate to problematic patterns of NMUPD, and whether they modify engagement in risky sexual behaviors. The objective of this study is to contribute directly to our understanding of the social factors that influence NMUPD and risky sexual behaviors among YMSM. The long-term goal of the study is to guide public health practitioners towards developing strategies that will prevent negative effects of NMUPD on YMSM, including reducing disparities in rates of HIV infection among YMSM. The study will investigate the central hypothesis of a deleterious relationship between NMUPD and physical, sexual, and psychological health of YMSM. The central hypothesis will be tested by pursuing three specific aims: Aim 1: Determine patterns of NMUPD and risky sexual behavior among YMSM in Philadelphia; Aim 2: Determine the risk and protective factors contributing to NMUPD and risky sexual behavior among YMSM; Aim 3: Explore the social contexts of NMPUD. Aims 1 and 2 will be addressed by recruiting 190 YMSM ages 18-29 in Philadelphia who have recently misused prescription drugs. Aim 3 will be addressed by selecting a subsample of 25 YMSM for a qualitative study. This approach is innovative because it utilizes a conceptual framework that combines a minority stress model and theories of social norms, social support, and resilience; it focuses on a critical cohort of under-researched, hard-to-reach population; and it employs two research methodologies. The proposed research is significant because it is expected to advance and expand our understanding of the effects of an emerging phenomena (i.e., prescription drug misuse) on adverse consequences of sexual activity. It will also contribute to a better understanding of the role of social determinants on dug use and risky sexual behavior. Such knowledge may inform the development of evidence-based strategies that will prevent adverse health and psychological effects of NMUPD on YMSM and their communities in Philadelphia and elsewhere in the U.S.